Elevated serum levels of bone sialoprotein during ICU treatment predict long-term mortality in critically ill patients

Mark Luedde,Frank Tacke,Pia Hoening,Martina Spehlmann,Tom Luedde,Norbert Frey,Alexander Koch,Christoph Roderburg,Mihael Vucur,Sanchari Roy,Sven Loosen,David Vargas Cardenas,Christian Trautwein,Hans-Joerg Hippe

doi:10.1038/s41598-018-28201-7

Mark Luedde, Frank Tacke + Show 12 more

Open Access

https://doi.org/10.1038/s41598-018-28201-7

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Abstract

Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family, has recently be associated to inflammatory and infectious diseases. We therefore measured BSP concentrations in 136 patients at admission to the intensive care unit (ICU) and 3 days of ICU. BSP levels were compared to 36 healthy blood donors and correlated to clinical data. In these analysis, BSP serum levels were strongly elevated at the time point of admission to the ICU when compared to healthy controls. Moreover BSP concentrations were significantly elevated after 3 days of treatment on the intensive care unit. A further increase in BSP levels was detected in patients with higher APACHE-II-scores and in patients with septic disease. While in most patients, BSP levels decreased during the first three days of treatment on a medical ICU, patients with persistently elevated BSP levels displayed an unfavorable outcome. In these patients, persistently elevated BSP concentrations were a superior predictor of mortality than established indicators of patient´ prognosis such as the SAPS2 or the APACHE-II score. In summary, our data argue for a novel utility for BSP as a biomarker in patients treated on a medical ICU.

Highlights

Bone sialoprotein (BSP), a member of the SIBLINGs family, has recently be associated to inflammatory and infectious diseases
The so called Small integrin-binding ligand N-linked glycoproteins (SIBLINGs)- family consists of five integrin-binding glycophosphoproteins, namely the bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), matrix extracellular phosphoglycoprotein (MEPE) and osteopontin (OPN)
A function of members of the SIBLINGs family was suggested in the regulation of inflammation and immunity, it is presently unknown if bone sialoprotein plays a functional role in systemic infections in intensive care unit (ICU) patients or if BSP might have a function as a biomarker in critically ill patients

Summary

Introduction

Bone sialoprotein (BSP), a member of the SIBLINGs (for Small Integrin-Binding LIgand, N-linked Glycoproteins) family, has recently be associated to inflammatory and infectious diseases. A function of members of the SIBLINGs family was suggested in the regulation of inflammation and immunity, it is presently unknown if bone sialoprotein plays a functional role in systemic infections in ICU patients or if BSP might have a function as a biomarker in critically ill patients. To address this question we measured BSP concentrations in the serum of critically ill patients that were treated on a large medical ICU within a tertiary referral center. We analyzed whether BSP measurements might serve marker indicating short- and long-term outcome in critical illness and sepsis

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